tbuckley/cabot-search huggingface dataset:
Physician Turnover in the United States
Authors: Amelia M. Bond, Lawrence P. Casalino, Ming Tai-Seale, Mark Aaron Unruh, Manyao Zhang, Yuting Qian, Richard Kronick
Journal: Annals of Internal Medicine (2023)

Background: Medical groups, health systems, and professional associations are concerned about potential increases in physician turnover, which may affect patient access and quality of care. Objective: To examine whether turnover has changed over time and whether it is higher for certain types of physicians or practice settings. Design: The authors developed a novel method using 100% of traditional Medicare billing to create national estimates of turnover. Standardized turnover rates were compared by physician, practice, and patient characteristics. Setting: Traditional Medicare, 2010 to 2020. Participants: Physicians billing traditional Medicare. Measurements: Indicators of physician turnover—physicians who stopped practicing and those who moved from one practice to another—and their sum. Results: The annual rate of turnover increased from 5.3% to 7.2% between 2010 and 2014, was stable through 2017, and increased modestly in 2018 to 7.6%. Most of the increase from 2010 to 2014 came from physicians who stopped practicing increasing from 1.6% to 3.1%; physicians moving increased modestly from 3.7% to 4.2%. Modest but statistically significant (P < 0.001) differences existed across rurality, physician sex, specialty, and patient characteristics. In the second and third quarters of 2020, quarterly turnover was slightly lower than in the corresponding quarters of 2019. Limitation: Measurement was based on traditional Medicare claims. Conclusion: Over the past decade, physician turnover rates have had periods of increase and stability. These early data, covering the first 3 quarters of 2020, give no indication yet of the COVID-19 pandemic increasing turnover, although continued tracking of turnover is warranted. This novel method will enable future monitoring and further investigations into turnover. Primary Funding Source: The Physicians Foundation Center for the Study of Physician Practice and Leadership.
Atrial Fibrillation
Authors: Sana M. Al-Khatib
Journal: Annals of Internal Medicine (2023)

Evidence for diagnosis and treatment of atrial fibrillation (AF) has expanded substantially since 2017, when In the Clinic last considered this subject. Direct oral anticoagulants have become the predominant therapy for thromboembolic disease, and antidotes for these drugs are now available. Device-based left atrial appendage occlusion is frequently used in patients who cannot tolerate systemic anticoagulation, and growing evidence suggests that early rhythm control improves outcomes. Catheter ablation is now frequently performed to prevent recurrent AF. Managing risk factors for AF, such as hypertension, diabetes, and obesity, remains paramount in prevention of this condition.
Risk of Left Atrial Thrombus in Patients With Hypertrophic Cardiomyopathy and Atrial Fibrillation
Authors: Daniel R. Burczak, Raghav R. Julakanti, Abdalla Kara Balla, Christopher G. Scott, Jeffrey B. Geske, Steve R. Ommen, Vuyisile T. Nkomo, Bernard J. Gersh, Peter A. Noseworthy, Konstantinos C. Siontis
Journal: Journal of the American College of Cardiology (2023)
Targeting the Androgen Signaling Axis in Prostate Cancer
Authors: Charles Dai, Scott M. Dehm, Nima Sharifi
Journal: Journal of Clinical Oncology (2023)

Activation of the androgen receptor (AR) and AR-driven transcriptional programs is central to the pathophysiology of prostate cancer. Despite successful translational efforts in targeting AR, therapeutic resistance often occurs as a result of molecular alterations in the androgen signaling axis. The efficacy of next-generation AR-directed therapies for castration-resistant prostate cancer has provided crucial clinical validation for the continued dependence on AR signaling and introduced a range of new treatment options for men with both castration-resistant and castration-sensitive disease. Despite this, however, metastatic prostate cancer largely remains an incurable disease, highlighting the need to better understand the diverse mechanisms by which tumors thwart AR-directed therapies, which may inform new therapeutic avenues. In this review, we revisit concepts in AR signaling and current understandings of AR signaling-dependent resistance mechanisms as well as the next frontier of AR targeting in prostate cancer.
Were cancer patients worse off than the general population during the COVID-19 pandemic? A population-based study from Norway, Denmark and Iceland during the pre-vaccination era
Authors: Anna L.V. Johansson, Anna Skog, Tom Børge Johannesen, Tor Åge Myklebust, Charlotte Wessel Skovlund, Lina Steinrud Mørch, Søren Friis, Mads Gamborg, Marnar Fríðheim Kristiansen, David Pettersson, Elínborg J. Ólafsdóttir, Helgi Birgisson, Runolfur Palsson, Elias Eythorsson, Sandra Irenaeus, Mats Lambe, Giske Ursin
Journal: The Lancet Regional Health - Europe (2023)

In a population-based setting, we investigated the risks of testing positive for SARS-CoV-2 and developing severe COVID-19 outcomes among cancer patients compared with the general population.In nationwide cohorts, we identified all individuals in Norway, Denmark and Iceland who tested positive for SARS-CoV-2 or had a severe COVID-19 outcome (hospitalisation, intensive care, and death) from March until December 2020, using data from national health registries. We estimated standardised incidence ratios (SIRs) with 95% confidence intervals (CIs) comparing cancer patients with the general population.During the first wave of the pandemic, cancer patients in Norway and Denmark had higher risks of testing SARS-CoV-2 positive compared to the general population. Throughout 2020, recently treated cancer patients were more likely to test SARS-CoV-2 positive. In Iceland, cancer patients experienced no increased risk of testing positive. The risk of COVID-19-related hospitalisation was higher among cancer patients diagnosed within one year of hospitalisation (Norway: SIR = 2.43, 95% CI 1.89-3.09; Denmark: 2.23, 1.96-2.54) and within five years (Norway: 1.58, 1.35-1.83; Denmark: 1.54, 1.42-1.66). Risks were higher in recently treated cancer patients and in those diagnosed with haematologic malignancies, colorectal or lung cancer. Risks of COVID-19-related intensive care and death were higher among cancer patients.Cancer patients were at increased risk of testing positive for SARS-CoV-2 during the first pandemic wave when testing availability was limited, while relative risks of severe COVID-19 outcomes remained increased in cancer patients throughout 2020. Recent cancer treatment and haematologic malignancy were the strongest risk factors.Nordic Cancer Union.
Reply to M. Roach et al and K.H. Stopsack et al
Authors: Andrew J. Vickers, Brandon Mahal, Olorunseun O. Ogunwobi
Journal: Journal of Clinical Oncology (2023)

Roach et al 1 claim that our arguments about the potential drivers of racial disparities in prostate cancer incidence and mortality are lacking in nuance and further speculate about the impact of our call to action to address cancer disparities. 2Our arguments were clear, supported by citations to empirical data, and nuanced in that we attribute excess mortality in prostate cancer disparities to racism, while incidence of disease appears to track with genetics, specifically West African ancestry.We summarized the existing data to make a call to action to address prostate cancer disparities, through appropriate efforts that may differ by incidence versus mortality.Our goal was to reduce prostate cancer morbidity and mortality in Black men. 2
Highlights From the <i>Circulation</i> Family of Journals
Authors: Christopher Ellis, Arnold Greenspon, John Andriulli, Paul Gould, Roger Carillo, Matthew Kolek, Rachel Donegan, Ansel Amaral, Suneet Mittal, Yasbanoo Moayedi, Eduard Rodenas-Alesina, Brigitte Mueller, Chun-Po Fan, Wida Cherikh, Josef Stehlik, Jeffrey Teuteberg, Heather Ross, Kiran Khush, Eric Hall, Colby Ayers, Ahmed Kolkailah, Christine Rutan, Jason Walchok, Joseph Williams, Tracy Wang, Fatima Rodriguez, Steven Bradley, Laura Stevens, Jennifer Hall, Pratheek Mallya, Gregory Roth, David Morrow, Mitchell Elkind, Sandeep Das, James De Lemos, Yu Kataoka, Stephen Nicholls, Rishi Puri, Satoshi Kitahara, Eri Kiyoshige, Kunihiro Nishimura, Kota Murai, Takamasa Iwai, Kenichiro Sawada, Hideo Matama, Satoshi Honda, Kensuke Takagi, Masashi Fujino, Shuichi Yoneda, Fumiyuki Otsuka, Kensaku Nishihira, Itaru Takamisawa, Yasuhide Asaumi, Teruo Noguchi, Ron Waksman, Sukhdeep Bhogal
Journal: Circulation (2023)

The May highlights from the Circulation family of journals span several topics in cardiovascular medicine.The results of a randomized trial to reduce pocket infections are presented in Circulation: Arrhythmia and Electrophysiology.Heart transplant outcomes among high-and low-risk donor and recipient characteristics are analyzed in Circulation: Heart Failure.The incidence of cardiovascular complications of COVID during the pandemic are reported in Circulation: Cardiovascular Quality and Outcomes.Sex-related differences in plaque composition in response to statin therapy are explored in Circulation: Cardiovascular Imaging.Finally, outcomes of leaflet thrombosis in low-risk patients receiving transcathether aortic valve replacement are reported in Circulation: Cardiovascular Interventions.
Myocardial Neprilysin Is Increased in Hypertrophic Cardiomyopathy
Authors: David W.J. Armstrong, Lance A. Riley, Yan Ru Su, Ashish S. Shah, Tarek Absi, Deepak K. Gupta, Quinn S. Wells, D. Marshall Brinkley, Lynne W. Stevenson, W. David Merryman
Journal: Circulation (2023)
Did covid-19 come from a lab leak in China?
Authors: Mun-Keat Looi
Journal: BMJ (2023)

Three and a half years since the pandemic began, the origins of covid-19 are back in the news. Mun-Keat Looi asks what the latest evidence means for the laboratory leak theory of covid As a mystery with no definitive answer, the story of the origin of covid-19 has almost never left media reports or the public consciousness in the three years since the pandemic began. Most recently, the US government declassified documents1 relating to its investigation into the origins of covid-19,2 while the Sunday Times reported documents and an interview with a former US government source.3 The Wall Street Journal also reported that three researchers who had been conducting coronavirus research at a controversial Wuhan laboratory in China (see box 1) were allegedly sick with signs of a respiratory illness at the end of 2019. And a BBC podcast about covid's possible beginnings4 featured rare public comments from the former head of China's infectious disease agency. Box 1 ### What is the laboratory leak theory of covid-19? This is the theory that instead of coming from a naturally occurring spillover from the animal kingdom, as most human diseases do, covid-19 may have been the result of a leak during laboratory experiments—either deliberately as an act of bioterrorism or accidentally because of bad laboratory safety practice. (Laboratory leaks do happen,6 although the vast majority are not of deadly pathogens.)7 Key to the credence given to the theory is the fact that the city where the first SARS-CoV-2 cases were detected is home to the Wuhan Institute of Virology (WIV), which conducts research into zoonotic diseases, including coronaviruses found in bats that are similar to SARS-CoV-2. Researchers at WIV had received funding from the US National Institute … RETURN TO TEXT
Healthy lifestyle and life expectancy free of major chronic diseases at age 40 in China
Authors: Qiufen Sun, Yizhen Hu, Canqing Yu, Yu Guo, Pei Pei, Ling Yang, Yiping Chen, Huaidong Du, Dianjianyi Sun, Yuanjie Pang, Sushila Burgess, Sam Sansome, Feng Ning, Junshi Chen, Zhengming Chen, Liming Li, Jun Lv
Journal: Nature Human Behaviour (2023)
AAV-mediated delivery of a Sleeping Beauty transposon and an mRNA-encoded transposase for the engineering of therapeutic immune cells
Authors: Lupeng Ye, Stanley Z. Lam, Luojia Yang, Kazushi Suzuki, Yongji Zou, Qianqian Lin, Yueqi Zhang, Paul Clark, Lei Peng, Sidi Chen
Journal: Nature Biomedical Engineering (2023)
Cxxc finger protein 1 maintains homeostasis and function of intestinal group 3 innate lymphoid cells with aging
Authors: Xin Shen, Xianzhi Gao, Yikai Luo, Qianying Xu, Ying Fan, Shenghui Hong, Zhengwei Huang, Xiaoqian Liu, Qianqian Wang, Zuojia Chen, Di Wang, Linrong Lu, Chuan Wu, Han Liang, Lie Wang
Journal: Nature Aging (2023)
ALK peptide vaccination restores the immunogenicity of ALK-rearranged non-small cell lung cancer
Authors: Ines Mota, Enrico Patrucco, Cristina Mastini, Navin R. Mahadevan, Tran C. Thai, Elisa Bergaggio, Taek-Chin Cheong, Giulia Leonardi, Elif Karaca-Atabay, Marco Campisi, Teresa Poggio, Matteo Menotti, Chiara Ambrogio, Dario L. Longo, Susan Klaeger, Hasmik Keshishian, Zsófia M. Sztupinszki, Zoltan Szallasi, Derin B. Keskin, Jonathan S. Duke-Cohan, Bruce Reinhold, Steven A. Carr, Catherine J. Wu, Kelly D. Moynihan, Darrell J. Irvine, David A. Barbie, Ellis L. Reinherz, Claudia Voena, Mark M. Awad, Rafael B. Blasco, Roberto Chiarle
Journal: Nature Cancer (2023)
Tumor monocyte content predicts immunochemotherapy outcomes in esophageal adenocarcinoma
Authors: Thomas M. Carroll, Joseph A. Chadwick, Richard P. Owen, Michael J. White, Joseph Kaplinsky, Iliana Peneva, Anna Frangou, Phil F. Xie, Jaeho Chang, Andrew Roth, Bob Amess, Sabrina A. James, Margarida Rei, Hannah S. Fuchs, Katy J. McCann, Ayo O. Omiyale, Brittany-Amber Jacobs, Simon R. Lord, Stewart Norris-Bulpitt, Sam T. Dobbie, Lucinda Griffiths, Kristen Aufiero Ramirez, Toni Ricciardi, Mary J. Macri, Aileen Ryan, Ralph R. Venhaus, Benoit J. Van den Eynde, Ioannis Karydis, Benjamin Schuster-Böckler, Mark R. Middleton, Xin Lu, David Ahern, Bob Amess, Kristen Aufiero Ramirez, Georgina Berridge, Thomas M. Carroll, Joseph A. Chadwick, Jaeho Chang, Jingfei Cheng, Sam T. Dobbie, Magdalena Drozdz, Roman Fischer, Anna Frangou, Hannah S. Fuchs, Lucinda Griffiths, Masato Inoue, Brittany-Amber Jacobs, Sabrina A. James, Joseph Kaplinsky, Ioannis Karydis, Benedikt M. Kessler, Simon R. Lord, Hantao Lou, Xin Lu, Mary J. Macri, Katy J. McCann, Naomi McGregor, Mark R. Middleton, Stewart Norris-Bulpitt, Ayo O. Omiyale, Richard P. Owen, Iliana Peneva, Chansavath Phetsouphanh, Margarida Rei, Toni Ricciardi, Andrew Roth, Carlos Ruiz Puig, Aileen Ryan, Benjamin Schuster-Böckler, Paulina Siejka-Zielińska, Chunxiao Song, Marketa Tomkova, Benoit J. Van den Eynde, Gergana Velikova, Ralph R. Venhaus, Michael J. White, Phil F. Xie
Journal: Cancer Cell (2023)

For inoperable esophageal adenocarcinoma (EAC), identifying patients likely to benefit from recently approved immunochemotherapy (ICI+CTX) treatments remains a key challenge. We address this using a uniquely designed window-of-opportunity trial (LUD2015-005), in which 35 inoperable EAC patients received first-line immune checkpoint inhibitors for four weeks (ICI-4W), followed by ICI+CTX. Comprehensive biomarker profiling, including generation of a 65,000-cell single-cell RNA-sequencing atlas of esophageal cancer, as well as multi-timepoint transcriptomic profiling of EAC during ICI-4W, reveals a novel T cell inflammation signature (INCITE) whose upregulation correlates with ICI-induced tumor shrinkage. Deconvolution of pre-treatment gastro-esophageal cancer transcriptomes using our single-cell atlas identifies high tumor monocyte content (TMC) as an unexpected ICI+CTX-specific predictor of greater overall survival (OS) in LUD2015-005 patients and of ICI response in prevalent gastric cancer subtypes from independent cohorts. Tumor mutational burden is an additional independent and additive predictor of LUD2015-005 OS. TMC can improve patient selection for emerging ICI+CTX therapies in gastro-esophageal cancer.
Therapeutic Potential of PTB Inhibition Through Converting Glial Cells to Neurons in the Brain
Authors: Xiang-Dong Fu, William C. Mobley
Journal: Annual Review of Neuroscience (2023)

Cell replacement therapy represents a promising approach for treating neurodegenerative diseases. Contrary to the common addition strategy to generate new neurons from glia by overexpressing a lineage-specific transcription factor(s), a recent study introduced a subtraction strategy by depleting a single RNA-binding protein, Ptbp1, to convert astroglia to neurons not only in vitro but also in the brain. Given its simplicity, multiple groups have attempted to validate and extend this attractive approach but have met with difficulty in lineage tracing newly induced neurons from mature astrocytes, raising the possibility of neuronal leakage as an alternative explanation for apparent astrocyte-to-neuron conversion. This review focuses on the debate over this critical issue. Importantly, multiple lines of evidence suggest that Ptbp1 depletion can convert a selective subpopulation of glial cells into neurons and, via this and other mechanisms, reverse deficits in a Parkinson's disease model, emphasizing the importance of future efforts in exploring this therapeutic strategy.
How Do You Build a Cognitive Map? The Development of Circuits and Computations for the Representation of Space in the Brain
Authors: Flavio Donato, Anja Xu Schwartzlose, Renan Augusto Viana Mendes
Journal: Annual Review of Neuroscience (2023)

In mammals, the activity of neurons in the entorhinal-hippocampal network is modulated by the animal's position and its movement through space. At multiple stages of this distributed circuit, distinct populations of neurons can represent a rich repertoire of navigation-related variables like the animal's location, the speed and direction of its movements, or the presence of borders and objects. Working together, spatially tuned neurons give rise to an internal representation of space, a cognitive map that supports an animal's ability to navigate the world and to encode and consolidate memories from experience. The mechanisms by which, during development, the brain acquires the ability to create an internal representation of space are just beginning to be elucidated. In this review, we examine recent work that has begun to investigate the ontogeny of circuitry, firing patterns, and computations underpinning the representation of space in the mammalian brain.
Cortical Integration of Vestibular and Visual Cues for Navigation, Visual Processing, and Perception
Authors: Sepiedeh Keshavarzi, Mateo Velez-Fort, Troy W. Margrie
Journal: Annual Review of Neuroscience (2023)

Despite increasing evidence of its involvement in several key functions of the cerebral cortex, the vestibular sense rarely enters our consciousness. Indeed, the extent to which these internal signals are incorporated within cortical sensory representation and how they might be relied upon for sensory-driven decision-making, during, for example, spatial navigation, is yet to be understood. Recent novel experimental approaches in rodents have probed both the physiological and behavioral significance of vestibular signals and indicate that their widespread integration with vision improves both the cortical representation and perceptual accuracy of self-motion and orientation. Here, we summarize these recent findings with a focus on cortical circuits involved in visual perception and spatial navigation and highlight the major remaining knowledge gaps. We suggest that vestibulo-visual integration reflects a process of constant updating regarding the status of self-motion, and access to such information by the cortex is used for sensory perception and predictions that may be implemented for rapid, navigation-related decision-making.
A Method of Human-Like Compliant Assembly Based on Variable Admittance Control for Space Maintenance
Authors: Xiaolei Cao, Xiao Huang, Yan Zhao, Zeyuan Sun, Hui Li, Zhihong Jiang, Marco Ceccarelli
Journal: Cyborg and Bionic Systems (2023)

On-orbit assembly has become a crucial aspect of space operations, where the manipulator frequently and directly interacts with objects in a complex assembly process. The traditional manipulator control has limitations in adapting to diverse assembly tasks and is vulnerable to vibration, leading to assembly failure. To address this issue, we propose a human-like variable admittance control method based on the variable damping characteristics of the human arm. By collecting the velocity and contact force of human arm operations in assembly, we analyze the damping change of human arm and establish the active compliance model based on S-type damping variation rule in assembly. Furthermore, 3 passive contact models are proposed between the end of the human arm and the environment: one-sided bevel contact, both sides bevel contact, and pin-hole contact. On the basis of these active and passive models, a typical space assembly task for a robot is designed, and a human-like variable admittance controller is established and simulated. Finally, we build a ground verification platform and complete different assembly tasks, thereby successfully verifying the safety, robustness, and adaptability of the human-like variable admittance control method.
Multiset correlation and factor analysis enables exploration of multi-omics data
Authors: Brielin C. Brown, Collin Wang, Silva Kasela, François Aguet, Daniel C. Nachun, Kent D. Taylor, Russell P. Tracy, Peter Durda, Yongmei Liu, W. Craig Johnson, David Van Den Berg, Namrata Gupta, Stacy Gabriel, Joshua D. Smith, Robert Gerzsten, Clary Clish, Quenna Wong, George Papanicolau, Thomas W. Blackwell, Jerome I. Rotter, Stephen S. Rich, R. Graham Barr, Kristin G. Ardlie, David A. Knowles, Tuuli Lappalainen
Journal: Cell Genomics (2023)

Multi-omics datasets are becoming more common, necessitating better integration methods to realize their revolutionary potential. Here, we introduce multi-set correlation and factor analysis (MCFA), an unsupervised integration method tailored to the unique challenges of high-dimensional genomics data that enables fast inference of shared and private factors. We used MCFA to integrate methylation markers, protein expression, RNA expression, and metabolite levels in 614 diverse samples from the Trans-Omics for Precision Medicine/Multi-Ethnic Study of Atherosclerosis multi-omics pilot. Samples cluster strongly by ancestry in the shared space, even in the absence of genetic information, while private spaces frequently capture dataset-specific technical variation. Finally, we integrated genetic data by conducting a genome-wide association study (GWAS) of our inferred factors, observing that several factors are enriched for GWAS hits and
Leukemic progenitor compartment serves as a prognostic measure of cancer stemness in patients with acute myeloid leukemia
Authors: Allison L. Boyd, Justin Lu, Cameron G. Hollands, Lili Alsostovar, Shiva Murali, Jennifer C. Reid, Wendy Ye, Sean Vandersluis, Paige Johnson, Amro ElRafie, Deanna P. Porras, Dimetri Xenocostas, Andrew Leber, Brian Leber, Ronan Foley, Michael Trus, Tobias Berg, Eri Kawata, Anargyros Xenocostas, Mickie Bhatia
Journal: Cell Reports Medicine (2023)

We systematically investigate functional and molecular measures of stemness in patients with acute myeloid leukemia (AML) using a cohort of 121 individuals. We confirm that the presence of leukemic stem cells (LSCs) detected through in vivo xenograft transplantation is associated with poor survival. However, the measurement of leukemic progenitor cells (LPCs) through in vitro colony-forming assays provides an even stronger predictor of overall and event-free survival. LPCs not only capture patient-specific mutations but also retain serial re-plating ability, demonstrating their biological relevance. Notably, LPC content represents an independent prognostic factor in multivariate analyses including clinical guidelines of risk stratification. Our findings suggest that LPCs provide a robust functional measure of AML, enabling quantitative and rapid assessment of a wide range of patients. This highlights the potential of LPCs as a valuable prognostic factor in AML management.